Immunology Quiz on T Cell Activation and Tolerance
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Questions and Answers

Which of the following can trigger self-reactive T cells to be activated according to the concept of molecular mimicry?

  • Immunosuppressive cytokines
  • Foreign antigens
  • Microbial antigens (correct)
  • Autoantibodies

    • Systemic lupus erythematosus (SLE) causes the immune system to attack healthy tissues.

    True (A)

    Name one mechanism that contributes to immune privilege in certain tissues.

    Lack of lymphatic drainage, blood barriers, or immunosuppressive cytokines.

    Apoptosis involves the activation of proteins called ______.

    <p>Caspases</p> Signup and view all the answers

    Match the following factors with their association to systemic lupus erythematosus (SLE):

    <p>Genetic = Linked to predisposition of disease Environmental = Exposure to certain triggers Hormonal = Related to fluctuations in hormone levels Certain medicines = May induce or aggravate the condition</p> Signup and view all the answers

    What is immune tolerance?

    <p>The failure of the immune system to respond aggressively to an epitope (A)</p> Signup and view all the answers

    Self-tolerance can be induced in both immature and mature lymphocytes.

    <p>True (A)</p> Signup and view all the answers

    What are the two types of immunological tolerance mentioned?

    <p>Central tolerance and peripheral tolerance</p> Signup and view all the answers

    What may happen to immature B cells if editing fails?

    <p>They may be deleted (B)</p> Signup and view all the answers

    In the thymus, T cells that recognize self antigens with high avidity are ______.

    <p>deleted</p> Signup and view all the answers

    Anergy occurs when developing B cells recognize self antigens weakly and become functionally responsive.

    <p>False (B)</p> Signup and view all the answers

    What happens to some self-reactive CD4+ T cells in the thymus?

    <p>They differentiate into regulatory T cells. (A)</p> Signup and view all the answers

    What is peripheral tolerance in T cells?

    <p>The mechanism that renders mature T cells incapable of responding to self antigens. (B)</p> Signup and view all the answers

    Anergy in T cells refers to their activation in response to an antigen.

    <p>False (B)</p> Signup and view all the answers

    What may happen to immature lymphocytes specific for self antigens in generative lymphoid organs?

    <p>They may be deleted, change specificity, or develop into regulatory lymphocytes.</p> Signup and view all the answers

    What are the two major factors that contribute to the development of autoimmunity?

    <p>genetic susceptibility and environmental triggers</p> Signup and view all the answers

    Match the following terms with their definitions:

    <p>Central tolerance = Occurs in generative lymphoid organs Peripheral tolerance = Involves mature lymphocytes becoming incapable of responding Self-reactive lymphocytes = Lymphocytes that recognize self antigens Regulatory T cells = Suppress immune responses against self antigens</p> Signup and view all the answers

    What are the two ligands recognized by PD-1?

    <p>PD-L1 and PD-L2</p> Signup and view all the answers

    Mature B lymphocytes that recognize self antigens in peripheral tissues may become functionally __________ or die by apoptosis.

    <p>unresponsive</p> Signup and view all the answers

    Match the following mechanisms of autoimmunity with their descriptions:

    <p>Defects in deletion = Failure to remove self-reactive cells Defective regulatory T cells = Impaired control of immune responses Defective apoptosis = Failure to eliminate harmful self-reactive lymphocytes Epitope spreading = Exacerbation of disease through exposure to other antigens</p> Signup and view all the answers

    Regulatory T cells produce IL-10 and ________, both of which inhibit immune responses.

    <p>TGF-β</p> Signup and view all the answers

    The process wherein mature lymphocytes die by ______ occurs during peripheral tolerance.

    <p>apoptosis</p> Signup and view all the answers

    Match the following T cell mechanisms with their functions:

    <p>CTLA-4 = Blocks CD28 engagement by B7 PD-1 = Inactivates T cells upon ligand binding IL-10 = Inhibits IL-12 production TGF-β = Inhibits T cell proliferation</p> Signup and view all the answers

    Which of the following statements about autoimmune diseases is true?

    <p>They can be systemic or organ-specific. (D)</p> Signup and view all the answers

    What is receptor editing in immature B lymphocytes?

    <p>The rearrangement of genes responsible for BCR expression. (D)</p> Signup and view all the answers

    One of the general mechanisms of autoimmune reactions is adequate function of inhibitory receptors.

    <p>False (B)</p> Signup and view all the answers

    What is the phenomenon called when an immune response against one self antigen leads to the activation of lymphocytes specific for other tissue antigens?

    <p>epitope spreading</p> Signup and view all the answers

    The engagement of inhibitory receptors on T cells generally promotes their activation.

    <p>False (B)</p> Signup and view all the answers

    What role do regulatory T cells play in the immune system?

    <p>They suppress self-reactive lymphocytes and inhibit immune responses.</p> Signup and view all the answers

    Flashcards

    Immune Tolerance

    A state where the immune system does not react aggressively to an epitope.

    Immune Self-tolerance

    The specific type of immune tolerance where the body's immune system doesn't attack its own cells and tissues.

    Central Tolerance

    Immature lymphocytes that recognize self-antigens are eliminated or inactivated in the bone marrow or thymus.

    Peripheral Tolerance

    Mature lymphocytes encountering self-antigens in the periphery are suppressed, inactivated, or deleted.

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    Central Tolerance in T Cells

    T cells that recognize self-antigens in the thymus are actively deleted as a safety mechanism.

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    Regulatory T Cells

    CD4+ T cells that recognize self-antigens in the thymus are not deleted but instead become regulatory T cells.

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    Peripheral Tolerance in Lymphocytes

    Mature lymphocytes in peripheral tissues that encounter self-antigens are either inactivated or deleted.

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    Autoimmunity

    A state where a person's immune system attacks its own tissues and organs.

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    B cell deletion

    Immature B cells that strongly recognize self-antigens are eliminated to prevent autoimmunity.

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    B cell anergy

    Immature B cells that weakly recognize self-antigens become unresponsive, preventing them from reacting against the body's own tissues.

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    Peripheral Tolerance in B Cells

    Mature B cells encountering self-antigens in peripheral tissues are either inactivated or destroyed, preventing autoimmune responses.

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    Inhibitory Receptors in B Cell Tolerance

    Inhibitory receptors on B cells act as safety switches, preventing activation unless there's a strong enough signal from a foreign antigen.

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    Genetic Susceptibility in Autoimmunity

    Genetic susceptibility plays a role in autoimmunity, making some individuals more prone to developing these conditions. These genes interact with environmental factors to trigger disease.

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    Infections and Autoimmunity

    Infections, especially viral and bacterial, can contribute to the development and worsening of autoimmune diseases.

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    Epitope Spreading

    When the immune system attacks one self-antigen, it can also trigger a wider response against other related antigens, making the autoimmune disease more severe.

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    Anergy (T Cell Functional Unresponsiveness)

    The inability of a T cell to respond to its specific antigen due to lack of costimulatory signals or innate immune input.

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    CTLA-4

    A protein receptor on T cells that binds to B7 molecules on antigen-presenting cells (APCs), preventing T cell activation.

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    PD-1

    Another inhibitory receptor on T cells that recognizes ligands PD-L1 and PD-L2 on APCs and other cells, leading to T cell inactivation.

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    Transforming Growth Factor-β (TGF-β)

    A cytokine that inhibits immune responses by suppressing T cell proliferation and effector functions, and also inhibiting macrophage activation.

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    Interleukin-10 (IL-10)

    A cytokine produced by regulatory T cells that inhibits the production of IL-12 by dendritic cells and macrophages, thus reducing IFN-γ production and suppressing the immune response.

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    Receptor Editing (B Cell Central Tolerance)

    A process by which immature B cells expressing self-reactive B cell receptors (BCRs) either rearrange their BCR genes to produce a modified receptor or are eliminated from the bone marrow.

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    Systemic Lupus Erythematosus (SLE)

    A state where the immune system mistakenly attacks healthy tissues and organs. It can affect skin, joints, kidneys, brain, and other organs.

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    Immune Privileged Tissues

    Sites in the body that are immune to pathogens, tumor cells, and tissue transplants. Foreign antigens are often tolerated in these areas.

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    Apoptosis

    The process of programmed cell death that is essential for removing damaged or infected cells from the body.

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    Extrinsic Apoptosis

    A type of apoptosis initiation that is triggered by external signals, such as death receptors on a cell's surface.

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    Intrinsic Apoptosis

    A type of apoptosis initiation that is triggered by internal factors within the cell, often a response to stress or damage.

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    Study Notes

    Immunological Tolerance and Autoimmunity

    • Immunological Tolerance: The immune system's failure to respond aggressively to an epitope.
    • Immune Self-tolerance: Results from inactivation or destruction of lymphocytes bearing BCRs and TCRs that recognize and bind self-antigens.

    General Features of Immunological Tolerance

    • Normal individuals tolerate their own antigens because lymphocytes recognizing self-antigens are killed, inactivated, or their specificity is altered.
    • Self-tolerance can develop in immature lymphocytes of generative lymphoid organs (central tolerance) or in mature lymphocytes in peripheral tissues (peripheral tolerance).
    • Central tolerance occurs during lymphocyte maturation in central lymphoid organs.
    • Peripheral tolerance happens when mature lymphocytes recognize self-antigens and lose their ability to respond or undergo apoptosis, or are actively suppressed by regulatory T cells.

    T Lymphocyte Tolerance: Central

    • During T cell maturation in the thymus, many immature T cells recognizing self-antigens with high avidity are deleted (negative selection).
    • Some self-reactive CD4+ T cells develop into regulatory T cells specific for these antigens in the thymus.

    T Lymphocyte Tolerance: Peripheral

    • Peripheral tolerance is the mechanism that renders mature T-cells recognizing self-antigens in peripheral tissues incapable of subsequent responses.
    • Costimulation failure or lack of innate immunity can render mature CD4+ T cells unresponsive (anergy).
    • Regulatory T cells can also suppress responses to self-antigens.

    T Lymphocyte Tolerance: Mechanisms

    • CTLA-4: A receptor of the CD28 family that inhibits T-cell responses by binding to B7 molecules with higher affinity than CD28 does.
    • PD-1: Recognizes two ligands (PD-L1 and PD-L2) expressed by APCs and other tissue cells, leading to T-cell inactivation.

    Suppression of Self-Reactive Lymphocytes by Regulatory T Cells

    • Regulatory T cells produce IL-10 and TGF-β, which inhibit immune responses.
    • TGF-β inhibits the proliferation and effector functions of T cells and activates macrophages. It also suppresses other cells like neutrophils.
    • IL-10 inhibits the production of IL-12 by activated dendritic cells and macrophages - inhibiting IFN-γ. It also stops costimulatory and Class II MHC molecules from being expressed on dendritic and macrophage cells.

    B Lymphocyte Tolerance: Central

    • Immature B cells recognizing self-antigens with high affinity in bone marrow either adjust their specificity or are eliminated.
    • Receptor editing: Genes responsible for BCR expression rearrange to produce a new receptor.
    • Deletion: If editing fails, immature B cells can be eliminated.
    • Anergy: Weakly self-reactive B cells become unresponsive (anergic) and leave the bone marrow.

    B Lymphocyte Tolerance: Peripheral

    • Mature B cells recognizing self-antigens in peripheral tissues may become unresponsive or undergo apoptosis in the absence of helper T cells.
    • Inhibitory receptors set a threshold for B cell activation.

    Autoimmunity

    • Autoimmunity results from a failure of self-tolerance mechanisms, leading to an imbalance in lymphocyte activation and control.
    • Defects in deletion (negative selection) of T or B cells, receptor editing in B cells, lack of regulatory T cells, or inadequate apoptotic functionality of self-reactive lymphocytes are potential causes.
    • Genetic susceptibility and environmental factors influence autoimmunity.

    Pathogenesis of Autoimmunity

    • Infections or injuries can trigger autoimmune diseases.

    • Autoimmune diseases can be systemic or organ-specific, depending on the distribution of the recognized autoantigens.

    • Autoimmune diseases are often chronic, progressive, or self-perpetuating.

    • Epitope spreading: A response to one self-antigen that damages tissue can cause other self-antigens to be released and cause the disease to worsen.

    • Most autoimmune diseases are a complex polygenic trait.

    • Microbes can activate Antigen-Presenting Cells (APCs) to show self-antigens and activate self-reactive T cells, thereby exacerbating the issue.

    • Some microbial antigens can cross-react with self-antigens (molecular mimicry).

    Immune Privileged Tissues

    • Certain body sites, such as the eye, testis, brain, placenta, and fetus, do not develop immune responses.
    • Mechanisms for immune privilege vary and include lack of lymphatic drainage, blood barriers, suppressive cytokines, and the expression of FasL and PD-L1.

    Apoptosis

    • Apoptosis is a regulated cell death process involved in physiological and pathological conditions.
    • Two pathways (extrinsic and intrinsic) initiate apoptosis leading to caspase activation.
    • Caspases fragment the nucleus and break down the cytoskeleton.

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    Immunological Tolerance and Autoimmunity PDF

    Description

    Test your knowledge on the mechanisms of T cell activation and the concept of immune tolerance, particularly in relation to systemic lupus erythematosus (SLE). This quiz covers topics such as molecular mimicry, immune privilege, and various forms of immunological tolerance affecting T cells and B cells. Dive into the intricacies of self-reactive T cells and their regulation in the immune system.

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